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| | ==Solution Structure and Molecular determinants of Hemoglobin Binding of the first NEAT Domain of IsdB in Staphylococcus aureus== | | ==Solution Structure and Molecular determinants of Hemoglobin Binding of the first NEAT Domain of IsdB in Staphylococcus aureus== |
| - | <StructureSection load='2moq' size='340' side='right' caption='[[2moq]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2moq' size='340' side='right'caption='[[2moq]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2moq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staaw Staaw]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MOQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2moq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_MW2 Staphylococcus aureus subsp. aureus MW2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MOQ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">isdB, frpB, sasJ, sirH, MW1011 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=196620 STAAW])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2moq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2moq OCA], [http://pdbe.org/2moq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2moq RCSB], [http://www.ebi.ac.uk/pdbsum/2moq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2moq ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2moq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2moq OCA], [https://pdbe.org/2moq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2moq RCSB], [https://www.ebi.ac.uk/pdbsum/2moq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2moq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISDB_STAAW ISDB_STAAW]] Seems to function as the primary receptor for hemoglobin since its inactivation inhibits the ability of S.aureus to bind hemoglobin. Binds hemoglobin in a dose-dependent way. Required for S.aureus growth using hemoglobin as the sole iron source. Also required for virulence (By similarity). IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils.<ref>PMID:18097052</ref> | + | [https://www.uniprot.org/uniprot/ISDB_STAAW ISDB_STAAW] Seems to function as the primary receptor for hemoglobin since its inactivation inhibits the ability of S.aureus to bind hemoglobin. Binds hemoglobin in a dose-dependent way. Required for S.aureus growth using hemoglobin as the sole iron source. Also required for virulence (By similarity). IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils.<ref>PMID:18097052</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Staaw]] | + | [[Category: Large Structures]] |
| - | [[Category: Copie, V]] | + | [[Category: Staphylococcus aureus subsp. aureus MW2]] |
| - | [[Category: Eilers, B J]] | + | [[Category: Copie V]] |
| - | [[Category: Fonner, B A]] | + | [[Category: Eilers BJ]] |
| - | [[Category: Lei, B]] | + | [[Category: Fonner BA]] |
| - | [[Category: Lui, M]] | + | [[Category: Lei B]] |
| - | [[Category: Moore, R]] | + | [[Category: Lui M]] |
| - | [[Category: Stanisich, J]] | + | [[Category: Moore R]] |
| - | [[Category: Sullivan-Springhetti, R K]] | + | [[Category: Stanisich J]] |
| - | [[Category: Tripet, B P]] | + | [[Category: Sullivan-Springhetti RK]] |
| - | [[Category: Hemoglobin receptor]]
| + | [[Category: Tripet BP]] |
| - | [[Category: Iron surface determinant protein]]
| + | |
| - | [[Category: Isdb]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Neat domain]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Staphylococcus aureus]]
| + | |
| Structural highlights
Function
ISDB_STAAW Seems to function as the primary receptor for hemoglobin since its inactivation inhibits the ability of S.aureus to bind hemoglobin. Binds hemoglobin in a dose-dependent way. Required for S.aureus growth using hemoglobin as the sole iron source. Also required for virulence (By similarity). IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils.[1]
Publication Abstract from PubMed
The human pathogen Staphylococcus aureus acquires heme iron from hemoglobin (Hb) via the action of a series of iron-regulated surface determinant (Isd) proteins. The cell wall anchored IsdB protein is recognized as the predominant Hb receptor, and is comprised of two NEAr transporter (NEAT) domains that act in concert to bind, extract, and transfer heme from Hb to downstream Isd proteins. Structural details of the NEAT 2 domain of IsdB have been investigated, but the molecular coordination between NEAT 2 and NEAT 1 to extract heme from hemoglobin has yet to be characterized. To obtain a more complete understanding of IsdB structure and function, we have solved the 3D solution structure of the NEAT 1 domain of IsdB (IsdBN1) spanning residues 125-272 of the full-length protein by NMR. The structure reveals a canonical NEAT domain fold and has particular structural similarity to the NEAT 1 and NEAT 2 domains of IsdH, which also interact with Hb. IsdBN1 is also comprised of a short N-terminal helix, which has not been previously observed in other NEAT domain structures. Interestingly, the Hb binding region (loop 2 of IsdBN1) is disordered in solution. Analysis of Hb binding demonstrates that IsdBN1 can bind metHb weakly and the affinity of this interaction is further increased by the presence of IsdB linker domain. IsdBN1 loop 2 variants reveal that phenylalanine 164 (F164) of IsdB is necessary for Hb binding and rapid heme transfer from metHb to IsdB. Together, these findings provide a structural role for IsdBN1 in enhancing the rate of extraction of metHb heme by the IsdB NEAT 2 domain.
Solution Structure and Molecular Determinants of Hemoglobin Binding of the First NEAT Domain of IsdB in Staphylococcus aureus.,Fonner BA, Tripet BP, Eilers BJ, Stanisich J, Sullivan-Springhetti RK, Moore R, Liu M, Lei B, Copie V Biochemistry. 2014 Jun 11. PMID:24871270[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Palazzolo-Ballance AM, Reniere ML, Braughton KR, Sturdevant DE, Otto M, Kreiswirth BN, Skaar EP, DeLeo FR. Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol. 2008 Jan 1;180(1):500-9. PMID:18097052
- ↑ Fonner BA, Tripet BP, Eilers BJ, Stanisich J, Sullivan-Springhetti RK, Moore R, Liu M, Lei B, Copie V. Solution Structure and Molecular Determinants of Hemoglobin Binding of the First NEAT Domain of IsdB in Staphylococcus aureus. Biochemistry. 2014 Jun 11. PMID:24871270 doi:http://dx.doi.org/10.1021/bi5005188
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